Histone chaperone FACT is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair, and also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.

Histone chaperone

FACT

Ssrp1

Chromatin accessibility

CTCF

Transcription

facilitates chromatin transcription

structure-specific recognition protein 1

suppressor of ty homolog 16

topologically associating domains

mouse embryonic fibroblast

transcription start site

DNA double-strand break

mouse embryonic stem cells

© 2023 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.